SBIR Phase I: A scalable high-throughput cell engineering platform

SBIR 第一阶段：可扩展的高通量细胞工程平台

• 批准号: 1747096
• 负责人: Paulo Garcia
• 金额: $ 22.5万
• 依托单位: Kytopen Corp
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1747096&HistoricalAwards=false
• 关键词: SBIR; Phase; scalable; throughput; cell

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) project is the development a scalable, automated, genetic transformation platform that is 10,000X faster than the current state-of-the-art. The fields of synthetic biology and genetic engineering are currently limited by the ability to re-program microorganisms with foreign DNA. There have been significant advances in the synthesis of DNA, screening of genetically engineered microorganisms, and bioinformatics. However, the technology used to deliver DNA and perform genetic transformation has not advanced in a similar way. Phase I of this SBIR will result in a prototype high-throughput genetic transformation platform to demonstrate the utility of the system. This system will allow genetic engineers to more rapidly develop microorganisms for the production of bioengineered chemicals and materials. This SBIR Phase I project proposes to develop a high-throughput, automated platform for genetic transformation of bacteria using a proprietary flow-through electroporation technology that is fast, reliable, and scalable. A key step in genetic engineering of cells is to introduce the foreign DNA that re-programs the cell. Electroporation, cell permeabilization using pulsed electric fields, is the most efficient and widespread method to deliver DNA into microorganisms for this application. State-of-the-art electroporation involves cuvettes that expose the cells and DNA to uniform electric fields. However, this process is currently slow, labor-intensive, and expensive. The proposed technology can be automated by augmenting existing liquid handling robots, and, when operated in parallel, may improve the genetic transformation rate by up to 10,000X compared to current methods. This will represent a paradigm shift in areas dependent upon genetic transformation where DNA delivery using electroporation is currently a major bottleneck. Ultimately, the goal is to address the need for a high-throughput genetic transformation platform to accelerate innovation in synthetic biology.

这个小企业创新研究（SBIR）项目更广泛的影响/商业潜力是开发一个可扩展的、自动化的遗传转化平台，比当前最先进的技术快10，000倍。合成生物学和基因工程领域目前受到用外源DNA重新编程微生物的能力的限制。在DNA的合成、基因工程微生物的筛选和生物信息学方面已经取得了重大进展。然而，用于传递DNA和进行遗传转化的技术并没有以类似的方式发展。该SBIR的第一阶段将产生一个原型高通量遗传转化平台，以证明该系统的实用性。该系统将使基因工程师能够更快地开发用于生产生物工程化学品和材料的微生物。SBIR第一阶段项目旨在开发一种高通量的自动化平台，用于使用快速，可靠和可扩展的专有流通电穿孔技术进行细菌遗传转化。细胞基因工程的关键步骤是引入重新编程细胞的外源DNA。电穿孔，使用脉冲电场的细胞透化，是用于该应用的将DNA递送到微生物中的最有效和最广泛的方法。最先进的电穿孔涉及将细胞和DNA暴露于均匀电场的比色皿。然而，这个过程目前是缓慢的，劳动密集型的，昂贵的。所提出的技术可以通过增强现有的液体处理机器人来实现自动化，并且当并行操作时，与当前方法相比，可以将遗传转化率提高高达10，000倍。这将代表依赖于遗传转化的领域的范式转变，其中使用电穿孔的DNA递送是目前的主要瓶颈。最终，目标是解决对高通量遗传转化平台的需求，以加速合成生物学的创新。